Azodicarbonamide (ADC) is widely used in manufacturing and also in food-processing in some countries. The use of ADC for foodstuffs including additive and packages has been suspended in EU. This attributed that ADC showed respiratory sensitization to occupational workers and formed semicarbazide (SEM) by thermal degradation. SEM, belonging to hydrazine derivatives, is mutagenic in a Salmonella strain and genotoxic both in vitro and in vivo. EFSA concluded that the threshold mechanism is applied for the carcinogenicity of SEM; however, ADC is not allowed to use for food in many countries. Considering the background that ADC was a listed additive for food packages in Japan, we first assessed genotoxicity of ADC based on literature. ADC is mutagenic in vitro but failed to occur gene mutation in mammalian cell systems. Besides, induction of DNA damage in rat hepatocytes was not detected. ADC caused chromosomal aberrations in vivo, but results were mixed. Concerning biological significance of in vitro mutagenicity along with lack of carcinogenicity studies, we conducted a transgenic rodent gene mutation assay (OECD TG488) to evaluate in vivo mutagenicity of ADC. In brief, Muta Mouse were administered ADC orally for 28 days up to 1,000 mg/kg bw per day, the maximum dose recommended by the test-guideline. Mutant frequencies in liver and glandular stomach of the ADC-treated animals were not significantly different from respective negative control animals. These results demonstrate that ADC is not mutagenic in vivo.
